‘Hidden’ Outcomes of Prematurity

Researchers in the laboratory of Marlowe Eldridge, MD, MSME, have found that young adults born prematurely but who are otherwise healthy may still have ventilatory impairments that manifest in low-oxygen environments.

A Surprising Response to Low Oxygen

In his lab, Dr. Eldridge (above, at left with scientists Melissa Bates, PhD, and Emily Farrell, PhD) takes an integrative approach to cardiopulmonary physiology.

As part of their work on “Comprehensive Characterization of Intrapulmonary Arteriovenous Pathways in Health,” a grant from the National Institutes of Health–National Heart, Lung and Blood Institute (NIH–NHLBI), the team was investigating pulmonary vascular responses to hypoxia (lower than normal oxygen) and hyperoxia (higher than normal oxygen) in healthy young adults born prematurely.

Interestingly, during exposure to hypoxia, the investigators noticed something unusual: one participant entered respiratory depression—the opposite of what normally happens in a healthy adult.

The team created an additional comprehensive study to investigate whether others in the cohort would have similar abnormal responses to low oxygen.

Those participants were recruited from The Newborn Lung Project, a longitudinal cohort study of premature infants born in Wisconsin and Iowa led by UW Population Health Sciences professor Mari Palta, PhD. Members of the project’s first cohort were born in the 1980s and are now in their early 20s.

Potential Hidden Health Issues

According to scientist Melissa Bates, PhD, earlier studies in rodents suggest that these ventilatory impairments may stem from abnormal development of carotid chemoreceptors, the cells that drive the breathing response to changes in arterial oxygen.

People who don’t have a robust drive to breathe in low-oxygen environments are at increased risk of altitude sickness, sleep-disordered breathing, and vulnerability to complications with certain types of anesthesia.

The study raises questions about potential hidden health issues in a population of adults who collectively survive severe prematurity. It also underscores the value of cohort studies like the Newborn Lung Project.

“These adults appear clinically normal; you don’t notice these abnormalities until they’re stressed,” Dr. Bates explained. “It’s an example of a critical developmental window, where certain exposures can have a lifelong impact on physiology.”

An Integrative Approach to Cardiopulmonary Physiology

“Ours is one of the few laboratories that takes an integrative approach to cardiopulmonary physiology, including heart, lungs, and breathing control,” Dr. Eldridge said. With that approach, investigators can consider the broader physiological context beyond specific biological structures.

Currently, the lab is focusing on other aims of the NIH grant: examining pulmonary vasoreactivity under certain physiologic conditions such as exercise, bronchopulmonary dysplasia (a chronic lung disease often found in very low-birth-weight infants) and high-altitude pulmonary edema.